Stable free nitroxyl radicals as oxidation catalysts and process for oxidation

ABSTRACT

The instant invention relates to stable free nitroxyl radicals of formula (I) at least one of the substituents R is —O. and the others are hydrogen or OH; X is —NR 1 R 2 , wherein R 1  and R 2  are independently hydrogen, C 1 -C 18 alkyl or together with the nitrogen atom to which they are bound from a 5 or 6 membered ring which may be further interrupted by an O atom. Further subjects of the invention are an oxidation process for alcohols to aldehydes or ketones or to carboxylic acids in the presence of a compound of formula (I) and the use of stable free nitroxyl radicals of formula (I) as oxidation catalysts.

[0001] The instant invention relates to stable free nitroxyl radicals.Stable free nitroxyl radicals are useful for a variety of industrialapplications, such as for example as stabilizers to prevent vinylaromatic monomers from premature polymerization during distillation orpurification, as polymerization regulators in controlled radicalpolymerization processes and as oxidation catalysts in heterogeneous andhomogenous oxidation reactions. They are particularly useful ascatalysts for the selective oxidation of alcohols to aldehydes orketones or to carboxylic acids using an alkali hypohalite as oxidizingagent. Consequently an oxidation process and the use of these stablefree nitroxyl radicals as oxidation catalysts are also subjects of theinvention.

[0002] Selectivity is of primary importance in oxidation processes.Further functional groups present in the molecule, such as, for example,double bonds, should generally not be affected under the conditionschosen. Often, the targeted oxidation of secondary alongside primaryalcohol functions or vice versa is desired, without the respective otherfunction being affected. In the synthesis of aldehydes from primaryalcohols, carboxylic acids are often formed as byproducts of theoxidation reaction (over-oxidation), and the oxidation of 1,2-diols orα-hydroxyketones is frequently accompanied by C—C cleavage reactions.

[0003] It is known that primary and secondary alcohols can be convertedinto the corresponding carbonyl compounds using aqueous sodiumhypochlorite solution in the presence of catalytic amounts of organicnitroxyl radicals (A. E. J. de Nooy, A. C. Besemer, H. van Bekkum,Synthesis, 1996, 1153).

[0004] It is also known, that alcohols can be oxidized by Cu(I) andoxygen in the presence of a nitroxyl radical(2,2,6,6-tetramethylpiperidin-1-oxyl, TEMPO). This is for exampledescribed by Semmelhack, M. F.; Schmid, Christopher R.; Cortes, DavidA.; Chou, Chuen S, Oxidation of alcohols to aldehydes with oxygen andcupric ion, mediated by nitrosonium ion in J. Am. Chem. Soc. (1984),106(11), 3374-6.

[0005] Hitherto such reactions—especially when2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) has been used—havepredominantly been carried out in homogeneous phase. The reactions werecarried out either stoichiometrically or catalytically in respect ofTEMPO or the oxidation product resulting therefrom. The working up ofthe reaction products in such processes often proves to be awkward andinvolved, since a great deal of effort is required to remove thecatalyst and its attendant products.

[0006] It has now, surprisingly, been found that specific cyclicoligomeric stable free nitroxyl radicals are ideal catalysts inhomogenous and heterogeneous oxidation reactions, which can easily beremoved from the reaction products.

[0007] Furthermore the instant compounds have high catalytic activityand excellent selectivity.

[0008] One subject of the invention is therefore a compound of formula(I)

[0009] wherein

[0010] at least one of the substituents R is —O. and the others arehydrogen or OH;

[0011] X is —NR₁R₂, wherein R₁ and R₂ are independently hydrogen,C₁-C₁₈alkyl or together with the nitrogen atom to which they are boundform a 5 or 6 membered ring which may be further interrupted by an Oatom;

[0012] HY is an organic or inorganic acid; and

[0013] n is 0 or a number from 1-4.

[0014] Preferably X is a structural element of formulae

[0015] Most preferably X is of formula (II).

[0016] Preferred is a compound of formula (I) wherein at least two ofthe substituents R are —O., more preferably 50 to 100% of thesubstituents R are —O.

[0017] Preferably HY is selected from the group consisting of a halogencontaining inorganic protonic acid, a phosphorous containing inorganicacid, a sulfur containing inorganic acid, a C₁-C₄alkyl carboxylic acid,or a perfluor C₁-C₄alkyl carboxylic acid or an aromatic carboxylic acid.More preferably HY is HCl, HClO₄, HBr, HPF₆, H₃PO₄, H₂SO₄, CF₃COOH,CH₃COOH, HCOOH or benzoic acid.

[0018] Particularly preferred compounds are those wherein n is 0.

[0019] The compounds may be prepared from the corresponding amineprecursors (R is H) which are for example described in U.S. Pat. No.4,442,250. When X is of formula (II), the amine precursor is acommercial product, Chimassorb® 966, sold by Ciba Specialty Chemicals.

[0020] The oxidation may be carried out in analogy to the oxidation of4-hydroxy-2,2,6,6-tetramethylpiperidine described in U.S. Pat. No.5,654,434 with hydrogen peroxide. Another also suitable oxidationprocess is described in WO 00/40550 using peracetic acid.

[0021] As described before the oxidation must not necessarily be carriedout until all piperidine nitrogen atoms are oxidized. It can be stoppedat many stages before, thus leading to a product mixture which containsNH, NOH and NO. moieties.

[0022] A subject of the invention is therefore a process for theselective oxidation of alcohols to ketones or to aldehydes in organicsolvents by means of an oxidizing agent, which comprises carrying outthe oxidation in the presence of a homogenous or heterogeneous oxidationcatalyst of formula (I).

[0023] A further subject of the invention is a process for the selectiveoxidation of alcohols to ketones or to carboxylic acids in aqueoussolvents by means of an oxidizing agent, which comprises carrying outthe oxidation in the presence of a homogenous or heterogeneous oxidationcatalyst of formula (I).

[0024] It is one of the advantages that the compound of formula (I) canbe protonated by inorganic acids and recovered from organic solvents bywashing out with water.

[0025] Examples for oxidation agents are oxygen containing organic orinorganic compounds.

[0026] Typical are organic peracids, such as peracetic acid, H₂O₂,hypohalites, halites, halides and oxygen itself or combinations of them.

[0027] Preferred is a process for the selective oxidation of alcohols toketones or to aldehydes or of alcohols to carboxylic acids by means ofperacetic acid, H₂O₂, hypohalites, halites, halides and oxygen itself orcombinations of them, under neutral or alkaline conditions or metal ionslike Cu(I), Cu(II), Ru (II), Co(II), Mn(II) and mixtures thereof andoxygen as oxidizing agent, which comprises carrying out the oxidation inthe presence of a homogenous or heterogeneous oxidation catalyst offormula (I).

[0028] The oxidation catalyst may also be a mixture of compounds offormula (I).

[0029] Preferably the oxidation catalyst Is added in an amount of from0.1 to 20%, more preferably from 0.5% to 10% and most preferably from0.5 to 5%, by weight, based on the alcohol used.

[0030] Generally, a process which comprises carrying out the oxidationby means of an alkali hypohalite under neutral or alkaline conditions ispreferred.

[0031] Preference is given to a process that uses as the alkalihypohalite LiOCl, NaOCl, KOCl, LiOBr, NaOBr or KOBr.

[0032] LiOCl, NaOCl and KOCl are especially preferred, NaOCl being moreespecially preferred.

[0033] The hypohalite, is preferably added in the form of an aqueoussolution to the alcohol to be oxidized. The concentration may varywithin a wide range and is preferably from 5% to 20% by weight,especially from 10 to 15% by weight, of active chlorine based on thealcohol to be oxidized.

[0034] Together with the oxidizing agent, the aqueous solution can berendered neutral or alkaline by means of a buffer. Preferred buffers areaqueous solutions of alkali or alkaline earth hydroxides, alkali oralkaline earth carbonates and the corresponding hydrogen carbonates andalkali or alkaline earth phosphates and the corresponding hydrogen anddihydrogen phosphates.

[0035] Alkali hydrogen carbonates are especially preferred, sodiumhydrogen carbonate being more especially preferred.

[0036] Preferably the process is carried out at a temperature of lessthan 30° C., more preferably at a temperature between 5° C. and 20° C.

[0037] The pH value of the aqueous oxidation solution after the additionof the desired buffer is in the range from 7 to 12, especially in therange from 8 to 11 and more especially in the range from 8 to 10.

[0038] The alcohol to be oxidized may be a monoalcohol, diol or apolyol, monomeric or polymeric like starch or pulp, water soluble orwater insoluble or molecules containing other functional groups besideshydroxy.

[0039] In the case of liquid alcohols, the reaction can be carried outwithout the addition of further solvents, but it can be advantageous tocarry out the oxidation in a higher dilution.

[0040] The compounds of formula (I) may also be used as polymerizationregulators in controlled free radical polymerization, as for exampledescribed in U.S. Pat. No. 5,322,912, as polymerization inhibitorsduring distillation or purification of vinyl aromatic monomers or asflame retardants.

PREPARATION EXAMPLES Example 1

[0041]

[0042] R═H, O° at least one is O°

[0043] In a 500 ml three necked flask 50 gr of CHIMASSORB® 966, toluene250 ml, and 42 g of potassium carbonate were added. The heterogeneousmixture was cooled at 5-10° C. and with vigorous stirring 72.5 g of asolution of peracetic acid (35%) in acetic acid was added slowly overabout 1 h. The reaction mixture was allowed to stand for 2 h at 5-10° C.and 10 g of potassium carbonate were added; after that the temperaturewas spontaneously allowed to rise to 25° C. and the reaction wascontinued for additional 2 h at 25-30° C.; after that the temperaturewas increased until to 50° C. and maintained for 1 h. The mixture wasthen concentrated under reduced pressure and the crude product waswashed with water and dried under vacuum. 44 g of the desiredrose-coloured product was obtained. In order to increase the purity ofthe nitroxyl product, the crystallization of unreacted CHIMASSORB® 966has been repeated four times in dichloromethane The organic layer hasthen concentrated and dried under vacuum; obtaining a rose colouredsolid having the following analytical data:

[0044] Melting range: 267-270° C.

[0045] Nitroxyl Yield by ESR: 95%

Example 2

[0046] In a flask 1 g of the product from example 1 was added to 100 gof a 37% solution of hydrochloric acid in water. The mixture was stirredfor 8 hours at room temperature, until a homogeneous yellow-colouredsolution was obtained. The water was evaporated and the remaining saltwas dried under vacuum.

EXAMPLES FOR THE USE AS CATALYST IN OXIDATION REACTIONS Example A

[0047] Use as Homogeneous Catalyst for Alcohol Oxidation in OrganicSolvents

[0048] In a flask 0.072 g (0.05 mmol) of the product from example 1, 2.5g (19.2 mmol) of 2-octanol and 10 ml of dichloromethane and 2.8 gr ofKHCO3 (20% sol.) were added; the heterogeneous mixture was cooled to10-15° C. then was dropped 13.8 g of an aqueous solution of NaOCl(10.5%). After 3 hours the crude organic layer was analyzed using GC:98.6% of 2-octanone was obtained as desired product.

Example B

[0049] Recovery of the Catalyst

[0050] The organic layer of the reaction mixture in Example A wasseparated from the aqueous phase and stirred with 10 ml of concentratedHCl (37% in water). After 30 minutes the colorless organic layer wasseparated from the slightly yellow colored aqueous phase. The water wasevaporated and the separated salt of the catalyst was dried undervacuum.

Example C

[0051] Use as Heterogeneous Catalyst for Alcohol Oxidation in OrganicSolvents

[0052] In a flask 0.072 g (0.05 mmol) of the product from example 1, 2.5g (19.2 mmol) of 2-octanol, 10 ml of toluene and 2.8 gr of KHCO3 (20%sol.) were added; the heterogeneous mixture was cooled to 10-15° C. thenwere added 13.2 g of an aqueous solution of NaOCl (10.5%). After 2 hoursthe crude organic layer was analyzed using GC and ¹H-¹³C-NMR and 100% of2-octanone was obtained as desired product. The catalyst was recoveredby filtration of the crude reaction mixture.

Example D

[0053] Use as Heterogeneous Catalyst for the Selective Oxidation ofPrimary Alcohols in Organic Solvents

[0054] In a flask 0.06 g (0.042 mmol) of the product from example 1, 2.5g (17.1 mmol) of 2-ethyl-1,3-hexane-diol and 10 ml of toluene wereadded; the heterogeneous mixture was cooled to 10-15° C. then wasdropped 9.8 g of an aqueous solution of NaOCl (13%) maintaining the pHbetween 8.5-9.5 using a water solution of NaHCO₃. After 2 hours thecrude organic layer was analyzed using GC and ¹H-¹³C-NMR and 77% of2-ethyls 3-hydroxy-hexanal was obtained as desired product. The catalystwas recovered by filtration of the crude reaction mixture.

Example E

[0055] Use as Heterogeneous Catalyst for the Oxidation of Alcohols inWater

[0056] In a flask 0.02 g (0.014 mmol) of the product from example 1,0.195 g (1.0 mmol) of methyl-α-D-glucopyranoside and 10 ml of water wereadded; the mixture was kept at room temperature then was dropped 8 ml ofan aqueous solution of NaOCl (0.5M) maintaining the pH at 9.5 using a0.12 M solution of NaOH. After 24 hours the crude organic layer wasanalyzed using HPLC. 96% of the carboxy acid was obtained as desiredproduct. The catalyst was recovered by filtration of the crude reactionmixture.

Example E

[0057] Use as Homogeneous Catalyst for the Oxidation of Alcohols inWater

[0058] In a flask 0.30 g (0.2 mmol) of the product from Example 2, 2.5 g(20.8 mmol) of diethyleneglycolmonomethylether and 10 ml of water wereadded; the mixture was cooled to 10-15° C. then was dropped 48 g of anaqueous solution of NaOCl (13%) maintaining the pH between 6-7 using awater solution of KH₂PO₄ After 4 hours the crude solution was analyzedusing GC and ¹H- and ¹³C-NMR. 95% of the carboxy acid was obtained asdesired product. The catalyst was recovered by precipitation at pH>8 andfiltration of the reaction mixture.

Example F

[0059] Use as Catalyst for the Oxidation of Alcohols in Absence ofSolvent

[0060] In a flask 125 μl (0.8 mmol) of the 2-octanol, 3.2 mg (8 mmol) ofthe product from example 1 and 2.86 ml NaOCl-solution (0.35M; 1.0 mmol;pH 9.1 with KHCO₃) were added; the mixture was maintained at roomtemperature under vigorously stirring. After one hour the crude organiclayer was analyzed using GC: 100% of 2-octanone was obtained as desiredproduct. The catalyst was recovered by filtration of the crude reactionmixture.

1. A compound of formula (I)

wherein at least one of the substituents R is —O. and the others arehydrogen or OH; X is —NR₁R₂, wherein R₁ and R₂ are independentlyhydrogen, C₁-C₁₈alkyl or together with the nitrogen atom to which theyare bound form a 5 or 6 membered ring which may be further interruptedby an O atom; HY is an organic or inorganic acid; and n is 0 or a numberfrom 1-4.
 2. A compound according to claim 1 wherein X is a structuralelement of formulae


3. A compound according to claim 1 wherein n is 0 and at least two ofthe substituents R are —O.
 4. A process for the selective oxidation ofalcohols to ketones or to aldehydes or of alcohols to carboxylic acidsby means of an oxidizing agent, which comprises carrying out theoxidation in the presence of a homogenous or heterogeneous oxidationcatalyst of formula (I).
 5. A process for the selective oxidation ofalcohols to ketones or to aldehydes or of alcohols to carboxylic acidsaccording to claim 4 by means of peracetic acid, H₂O₂, hypohalites,halites, halides and oxygen itself or combinations of them, underneutral or alkaline conditions or metal ions like Cu(I), Cu(II), Ru(II), Co(II), Mn(II) and mixtures thereof and oxygen as oxidizing agent,which comprises carrying out the oxidation in the presence of ahomogenous or heterogeneous oxidation catalyst of formula (I).
 6. Aprocess according to claim 5, which comprises adding the oxidationcatalyst in an amount of from 0.1 to 20% by weight, based on the alcoholused.
 7. A process according to claim 5, which comprises carrying outthe oxidation by means of an alkali hypohalite selected from LiOCl,NaOCl, KOCl, LiOBr, NaOBr or KOBr under neutral or alkaline conditions.8. A process according to claim 5, which comprises carrying out thereaction at a temperature of less than 30° C. and at a pH of between 7and
 12. 9. The use of a compound of formula (I) as catalyst for theselective oxidation of alcohols to ketones or aldehydes or to carboxylicacids.
 10. The use of a compound of formula (I) as polymerizationregulator in controlled free radical polymerization, as polymerizationinhibitor during distillation or purification of vinyl aromatic monomersor as flame retardant.